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Figure 4.
Characterization of the IDE-insulin interaction. A, details
of the interaction between insulin and IDE. Additional hydrogen
bond networks are shown in the three right panels for clarity.
IDE and insulin are colored as in Fig. 3. B, comparison of
insulin in its free T-state form (PDB code 1G7A) and IDE-bound
form. C, comparison of surface charge distribution of the
partially unfolded insulin in insulin-bound IDE with T-state
insulin modeled into the catalytic chamber of IDE. Surface
representation of the substrate binding chamber of IDE was
generated by the software Voidoo (31). The outer surface of IDE
and the substrate chamber are colored pale green and dark green.
The electrostatic surface representations of the IDE-bound
insulin and T-state insulin models are calculated by Adaptive
Poisson-Boltzmann Solver. D, comparison of IDE-bound insulin
structure with the solution structures of insulin Ala^A2-DKP.
Insulin Ala^A2-DKP has an Ile to Ala mutation in A2 residue of
insulin-DKP, which is an engineered monomeric insulin. Left
shows the comparison of IDE-bound insulin (colored in red and
salmon for insulin A and B chain, respectively) with an
exemplary NMR structure of insulin Ala^A2-DKP (PDB code 1K3M;
colored in green and lime green for insulin A and B chain,
respectively), and an exemplary NMR structure of insulin-DKP
(PDB code 2JMN; colored in blue and light blue for insulin A and
B chain, respectively). For a fair comparison, solution
structures of insulin Ala^A2-DKP and insulin-DKP are also shown
in the middle and right, respectively.
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